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Journal of veterinary pharmacology and therapeutics2015; 39(3); 255-263; doi: 10.1111/jvp.12276

A quantitative approach to analysing cortisol response in the horse.

Abstract: The cortisol response to glucocorticoid intervention has, in spite of several studies in horses, not been fully characterized with regard to the determinants of onset, intensity and duration of response. Therefore, dexamethasone and cortisol response data were collected in a study applying a constant rate infusion regimen of dexamethasone (0.17, 1.7 and 17 μg/kg) to six Standardbreds. Plasma was analysed for dexamethasone and cortisol concentrations using UHPLC-MS/MS. Dexamethasone displayed linear kinetics within the concentration range studied. A turnover model of oscillatory behaviour accurately mimicked cortisol data. The mean baseline concentration range was 34-57 μg/L, the fractional turnover rate 0.47-1.5 1/h, the amplitude parameter 6.8-24 μg/L, the maximum inhibitory capacity 0.77-0.97, the drug potency 6-65 ng/L and the sigmoidicity factor 0.7-30. This analysis provided a better understanding of the time course of the cortisol response in horses. This includes baseline variability within and between horses and determinants of the equilibrium concentration-response relationship. The analysis also challenged a protocol for a dexamethasone suppression test design and indicated future improvement to increase the predictability of the test.
Publication Date: 2015-11-06 PubMed ID: 26542753DOI: 10.1111/jvp.12276Google Scholar: Lookup
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  • Clinical Trial
  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research article is looking at the cortisol response in horses to better understand how it behaves under different conditions. They used dexamethasone to stimulate the cortisol, and their findings offer insights into how this response can be used for testing purposes.

Research Background and Methodology

  • The researchers sought to better understand the cortisol response, specifically in horses, to glucocorticoid intervention through analyzing data from a study where varying levels of dexamethasone were administered to Standardbred horses. Types of responses assessed included the onset, intensity, and duration.
  • Three varying amounts of dexamethasone were used: 0.17, 1.7, and 17 μg/kg, and were introduced to the test animals through a constant rate infusion approach.
  • The cortisol and dexamethasone in the plasma were measured and analyzed using Ultra High-Performance Liquid Chromatography coupled with Tandem Mass Spectrometry (UHPLC-MS/MS), a cutting-edge analytical tool best suited for detecting and quantifying compounds in biological samples.

Results and Findings

  • The behavior of dexamethasone was found to be linear within the defined concentration range. This means as the dosage of this drug increased, so did the respective response.
  • The turnover model of oscillatory behavior was found to be a good fit for capturing the cortisol behavior. Changes in cortisol levels fluctuated in a regular pattern mimicking an oscillating system.
  • Specific numeric data was provided for baseline concentration range, the fractional turnover rate, the amplitude parameter, the maximum inhibitory capacity, drug potency, and the sigmoidicity factor.
  • The study found there was baseline variability within and between horses, suggesting individual differences in response. These findings are important for understanding the equilibrium concentration-response relationship.

Conclusions and Implications

  • The research provides a better understanding of the time course of the cortisol response in horses. This understanding could be used to inform future research or testing involving this response.
  • The study serves as an impetus to reconsider the dexamethasone suppression test design. The researchers suggested revisions that could increase the predictability of the test and improve the accuracy of results.

Cite This Article

APA
Ekstrand C, Ingvast-Larsson C, Olsén L, Hedeland M, Bondesson U, Gabrielsson J. (2015). A quantitative approach to analysing cortisol response in the horse. J Vet Pharmacol Ther, 39(3), 255-263. https://doi.org/10.1111/jvp.12276

Publication

ISSN: 1365-2885
NlmUniqueID: 7910920
Country: England
Language: English
Volume: 39
Issue: 3
Pages: 255-263

Researcher Affiliations

Ekstrand, C
  • Department of Biomedical Sciences and Veterinary Public Health, Division of Pharmacology and Toxicology, Swedish University of Agricultural Sciences, Uppsala, Sweden.
Ingvast-Larsson, C
  • Department of Biomedical Sciences and Veterinary Public Health, Division of Pharmacology and Toxicology, Swedish University of Agricultural Sciences, Uppsala, Sweden.
Olsén, L
  • Department of Biomedical Sciences and Veterinary Public Health, Division of Pharmacology and Toxicology, Swedish University of Agricultural Sciences, Uppsala, Sweden.
Hedeland, M
  • Department of Chemistry, Environment and Feed Hygiene, National Veterinary Institute (SVA), Uppsala, Sweden.
  • Department of Medicinal Chemistry, Division of Analytical Pharmaceutical Chemistry, Uppsala University, Uppsala, Sweden.
Bondesson, U
  • Department of Chemistry, Environment and Feed Hygiene, National Veterinary Institute (SVA), Uppsala, Sweden.
  • Department of Medicinal Chemistry, Division of Analytical Pharmaceutical Chemistry, Uppsala University, Uppsala, Sweden.
Gabrielsson, J
  • Department of Biomedical Sciences and Veterinary Public Health, Division of Pharmacology and Toxicology, Swedish University of Agricultural Sciences, Uppsala, Sweden.

MeSH Terms

  • Animals
  • Dexamethasone / administration & dosage
  • Dexamethasone / blood
  • Dexamethasone / pharmacology
  • Female
  • Glucocorticoids / administration & dosage
  • Glucocorticoids / blood
  • Glucocorticoids / pharmacology
  • Horses / blood
  • Hydrocortisone / blood
  • Male

Citations

This article has been cited 5 times.
  1. Ekstrand C, Pettersson H, Gehring R, Hedeland M, Adolfsson S, Lilliehöök I. Prednisolone in Dogs-Plasma Exposure and White Blood Cell Response. Front Vet Sci 2021;8:666219.
    doi: 10.3389/fvets.2021.666219pubmed: 34179161google scholar: lookup
  2. Ekstrand C, Bondesson U, Giving E, Hedeland M, Ingvast-Larsson C, Jacobsen S, Löfgren M, Moen L, Rhodin M, Saetra T, Ranheim B. Disposition and effect of intra-articularly administered dexamethasone on lipopolysaccharide induced equine synovitis. Acta Vet Scand 2019 Jun 20;61(1):28.
    doi: 10.1186/s13028-019-0464-2pubmed: 31221173google scholar: lookup
  3. Held F, Ekstrand C, Cvijovic M, Gabrielsson J, Jirstrand M. Modelling of oscillatory cortisol response in horses using a Bayesian population approach for evaluation of dexamethasone suppression test protocols. J Pharmacokinet Pharmacodyn 2019 Feb;46(1):75-87.
    doi: 10.1007/s10928-018-09617-0pubmed: 30673914google scholar: lookup
  4. Yu R, Jusko WJ. Meta-Analysis and Mechanism-Based Modeling of Synovial and Plasma Pharmacokinetics and Adrenal Suppression Following Intra-Articular Injection of Methylprednisolone Acetate in Horses. J Vet Pharmacol Ther 2025 Jul;48(4):260-273.
    doi: 10.1111/jvp.13504pubmed: 40059579google scholar: lookup
  5. Gabrielsson J, Hjorth S. Pattern Recognition in Pharmacodynamic Data Analysis. AAPS J 2016 Jan;18(1):64-91.
    doi: 10.1208/s12248-015-9842-5pubmed: 26542613google scholar: lookup